Streptococcus mutans, which is strongly implicated in caries causation, will be studied by genetic, experimental pathology, and regulatory-biochemical approaches. Several, hypothesized sucrose-associated, caries-linked traits to be investigated are: glucan synthesis, extracellular fructan production and utilization, sucrose permease and invertase activity, phosphate avidity, lactic acidogenesis and aciduricity, and intracellular polysaccharide production. These properties are germane to his bacterium's virulence and hence to elucidating traits responsible for dental caries. Wild type, virulent strains of S. mutans will be mutagenized and variants isolated for study. Conventional and/or gnotobiotic rats will be infected with mutants defective in one of the above pathways, thus permitting the correlation of specific genetic defects with the broader manifestation of virulence. Glucan-mediated adhesivity will be further investigated in two ways. The first is by analysis of glucosyl transferase enzyme profiles with a novel technique based on enzyme affinity for end-product. Insoluble glucans, strongly implicated in plaque formation, will be used to selectively purify their biosynthetic enzymes, allowing comparison of profiles between virulent, adhesive wild type and mutants. The second approach is the in vitro transformation of a non-virulent, non-adhesive, competent, group H streptococcus with DNA from wild type S. mutans which bears "adhesivity" genes. A more precise correlation between adhesion and virulence will follow from in vivo assay of adhesive transformants. Because sucrose is central both to caries causation and to the hypothesized caries-related traits of S. mutans, regulation of the catabolic and biosynthetic flow of sucrose carbon between two intracellular pathways will be studied from a metabolic-control viewpoint. Energy-yielding pathways in S. mutans compete for available carbohydrate with energy-consuming, biosynthetic systems such as the one elaborating intracellular polysaccharide. Study of competing enzyme activities, mediated by pathway intermediates, will clarify S. mutans' ability to persist in the oral ecology. The net result of the interaction of the genome of S. mutans with its environment is the destruction of the teeth, virulence.